Glycyrrhizin is a pharmaceutically active ingredient which is appreciated as a therapeutic agent for hepatic diseases and for allergy, and a medically essential drug due to its excellent improving action for hepatic functions, especially in the therapy of chronic hepatic diseases. At present, two kinds of clinically used glycyrrhizin-containing preparations, i.e., injection preparations and oral tablets, are available. In view of efficacy, the use of injection preparations is overwhelming. In the case of tablets, it has been reported that glycyrrhizin is quickly decomposed into glycyrrhetinic acid in the stomach, that transfer of unchanged glycyrrhizin having a high pharmacological activity into blood is hardly observed and accordingly that its effect is far poor as compared with injection preparations (Minophagen Medical Review, Extra Issue No.30, page 1 (1993)).
However, in the case of injection preparations, a dosage level for each administration is as high as 40-100 ml. It compels pain to the patient and, moreover, causes a lot of burden including hospitalization for long time or necessity of visiting the hospital for injection every day or several days a week to the patient in the case of chronic hepatic diseases requiring a therapy for a long period. Therefore, the use of suppositories or oral preparations as substitutes for injection preparations has been proposed where the improvement of absorption is attempted.
For instance, there have been proposals for suppositories, such as a suppository where a conventionally known base such as Witepsol H-15 is used (JP, 1-294619, A (1989)), a suppository where at least one kind of nonionic surface-active agents or medium-chain fatty acids is admixed as an absorption enhancer (JP, 4-261117, A (1992)) and a suppository where a nonionic surface-active agent is admixed, as an absorption enhancer, with an oleaginous base (JP, 5-97680, A (1993)). For oral preparations with an object of improvement in absorption, the following has been proposed: a preparation where fatty acid glyceride is admixed followed by coating with an enteric film (JP, 3-255037, A (1991)) and a preparation where glycyrrhizin is made into a fat emulsion, a mixture with a conjugated lipid, or dry powders thereof (JP, 6-192107, A (1994)).
However, those conventional preparations have disadvantages as described hereinbelow.
For the above-mentioned suppositories, it takes a long therapeutic term to treat chronic hepatic diseases as mentioned already, and the use of suppositories for a long period therefore compels a considerable burden on the patient although it will not be so much as in the case of injection preparations.
Further, for the above-mentioned oral preparations, the prior art example as disclosed in JP, 3-255037, A (1991) is discussed because the prior art oral preparation is administered to rats intraduodenally instead of orally in which glycyrrhizin is merely dispersed in a fatty acid glyceride mixture and consequently the concentration of glycyrrhizin in blood is measured whereby there are no data which scientifically and clearly support the oral efficacy of the disclosed preparation.
For the next prior art example as disclosed in JP, 6-192107, A (1994), a fat emulsion or conjugated lipid mixture of glycyrrhizin is prepared therein. Unlike solid preparations such as tablets, however, such a liquid preparation inherently has an anxiety of stability and its handling is also inconvenient. Even if such an emulsified preparation is dried and made into powders, steps for manufacturing such a preparation are quite complicated.
As such, at the level of the conventional art, it is difficult to prepare an oral preparation of glycyrrhizin causing little burden to patients and having the excellent property of being well absorbed from the digestive tract.